Department of Veterinary Medicine

Research in Veterinary Medicine

Research description

Recent research in my group is focused on the study of pathogenesis and immunity to bacterial infections and on the improvement of strategies to deliver vaccines to the immune system. We concurrently run a number of multidisciplinary integrated research projects. Our past research has defined the role of cytokine networks, antibodies and T-cell in host resistance to bacterial infections and has unravelled many bacterial virulence genes that counteract the immune system. This work is still evolving and has already contributed to the generation of new vaccine candidatesthat are currently being tested in trials. Recently, we have focused on understanding how individual bacteria interact with host cells in vivo and how subpopulations of microbes spread and distribute in the body. This has been achieved by novel multidisciplinary research approaches that integrate information acquired at different levels spanning from individual cells to global systems. This work has opened the possibility to comprehensively study the mechanistic bases of immune control of bacterial infections, thus opening the field to novel high impact research on improved prevention measures to fight infection. We are also exploring other new areas within infection such as the interplay between microbes and autoimmune diseases and the possibility to use recombinant bacteria as anti-cancer agents. This research may have translational outcomes in the generation of tools to modulate the course of autoimmune diseases and to distroy cancer cells in vivo. Another crucial line of research that we are actively pursuing deals with the understanding of how different cellular population and cell-surface receptors co-operate for the initiation and expansion of immune responses. This research is providing clues on what is required from bacterial vaccines to be effective and is guiding the development and testing of new vaccine preparations in human and domestic animals.

Main collaborators

• Gordon Dougan, Sanger Institute, Hinxton, UK
• Sjef Verbeek, University of Leiden, NL
• David Gray, University of Edinburgh, UK
• Anne Cooke, University of Cambridge, UK
• Anjam Khan, University of Newcastle, UK

Representive Selected publications since 2000

• Vazquez-Torres, A., Y. Xu, J. Jones-Carson, D. W. Holden, S. M. Lucia, M. C. Dinauer, P. Mastroeni and F. C. Fang (2000). Salmonella pathogenicity island 2-dependent evasion of the phagocyte NADPH oxidase. Science 287(5458): 1655-8. [PubMed]
• Vazquez-Torres, A., J. Jones-Carson, P. Mastroeni, H. Ischiropoulos and F. C. Fang (2000). Antimicrobial actions of the NADPH phagocyte oxidase and inducible nitric oxide synthase in experimental salmonellosis. I. Effects on microbial killing by activated peritoneal macrophages in vitro. J Exp Med 192(2): 227-36. [PubMed]
• Raine, T., P. Zaccone, P. Mastroeni and A. Cooke (2006). Salmonella typhimurium infection in nonobese diabetic mice generates immunomodulatory dendritic cells able to prevent type 1 diabetes. J Immunol 177(4): 2224-33. [PubMed]
• Brown, S. P., S. J. Cornell, M. Sheppard, A. J. Grant, D. J. Maskell, B. T. Grenfell and P. Mastroeni (2006). Intracellular demography and the dynamics of Salmonella enterica infections. PLoS Biol 4(11): e349. [PubMed]
• Menager, N., G. Foster, S. Ugrinovic, H. Uppington, S. Verbeek and P. Mastroeni (2007). Fcgamma receptors are crucial for the expression of acquired resistance to virulent Salmonella enterica serovar Typhimurium in vivo but are not required for the induction of humoral or T-cell-mediated immunity. Immunology 120(3): 424-32. [PubMed]
• Foster, G. L., T. A. Barr, A. J. Grant, T. J. McKinley, C. E. Bryant, A. MacDonald, D. Gray, M. Yamamoto, S. Akira, D. J. Maskell and P. Mastroeni (2008). Virulent Salmonella enterica infections can be exacerbated by concomitant infection of the host with a live attenuated S. enterica vaccine via Toll-like receptor 4-dependent interleukin-10 production with the involvement of both TRIF and MyD88. Immunology 124(4): 469-79. [PubMed]
• Grant, A. J., O. Restif, T. J. McKinley, M. Sheppard, D. J. Maskell and P. Mastroeni (2008). Modelling within-host spatiotemporal dynamics of invasive bacterial disease. PLoS Biol 6(4): e74. [PubMed]
• Barr, T. A., S. Brown, P. Mastroeni and D. Gray (2009). B cell intrinsic MyD88 signals drive IFN-gamma production from T cells and control switching to IgG2c. J Immunol 183(2): 1005-12. [PubMed]
• Mastroeni, P., A. Grant, O. Restif and D. Maskell (2009). A dynamic view of the spread and intracellular distribution of Salmonella enterica. Nat Rev Microbiol 7(1): 73-80. [PubMed]